From the beginning of their lives, cancer cells exert a procoagulant activity in their microenvironment, which can extend systemically and become clinically evident as Trousseau's syndrome, the well-known association between tumor and thrombosis. It is becoming clear that the genetic mechanisms responsible for neoplastic transformation (activation of oncogenes such as RAS or MET, and inactivation of tumor suppressor genes such as p53 or PTEN) directly induce the expression of genes controlling hemostasis. Activation of blood coagulation results in a selective advantage for cancer cells, as fibrin provides a scaffold for anchorage and invasion, and coagulation proteins induce receptor-mediated intracellular signals promoting invasive growth. Targeting the tumor procoagulant activity can fight not only a dangerous tumor adverse effect, but also the core mechanisms of cancer onset and progression.